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Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders.
Sampah, MES, Hackam, DJ
Frontiers in immunology. 2021;:650709
Abstract
Prior to birth, the neonate has limited exposure to pathogens. The transition from the intra-uterine to the postnatal environment initiates a series of complex interactions between the newborn host and a variety of potential pathogens that persist over the first few weeks of life. This transition is particularly complex in the case of the premature and very low birth weight infant, who may be susceptible to many disorders as a result of an immature and underdeveloped immune system. Chief amongst these disorders is necrotizing enterocolitis (NEC), an acute inflammatory disorder that leads to necrosis of the intestine, and which can affect multiple systems and have the potential to result in long term effects if the infant is to survive. Here, we examine what is known about the interplay of the immune system with the maternal uterine environment, microbes, nutritional and other factors in the pathogenesis of neonatal pathologies such as NEC, while also taking into consideration the effects on the long-term health of affected children.
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Prevention of Gestational Diabetes Mellitus (GDM) and Probiotics: Mechanism of Action: A Review.
Homayouni, A, Bagheri, N, Mohammad-Alizadeh-Charandabi, S, Kashani, N, Mobaraki-Asl, N, Mirghafurvand, M, Asgharian, H, Ansari, F, Pourjafar, H
Current diabetes reviews. 2020;(6):538-545
Abstract
BACKGROUND Gestational Diabetes Mellitus (GDM) is a health problem that is increasing around the world. INTRODUCTION Prevention of GDM, rather than treatment, could have several benefits in terms of both health and economic cost. Even a slight reduction in maternal glucose in non-diabetic women, particularly in women at high risk for GDM, may have significant benefits for pregnancy results and the future health of off-springs. Probiotics are a relatively new intervention, which are assessed by mothers' metabolism, and can reduce blood sugar levels, prevent gestational diabetes and reduce the maternal and fetal complications resulting from it. The aim of this study was to review the studies on the prevention of gestational diabetes and assess the potential beneficial effects of probiotics on gestational diabetes and their possible mechanism of action. METHODS Articles compiled through clinical trials indexed in PubMed, Science Direct, Cochran, and Medlib between 2000 and 2017, with the keywords probiotics, prevention, and gestational diabetes mellitus were selected. RESULTS Considering the potential of probiotics in the modulation of gut microbiota, naturalization increases intestinal permeability, regulation of pro-inflammatory mediators' secretion and thereby controlling local and systemic inflammation results in decreasing intestinal permeability, enhancing the immune system. It likely has the ability to prevent or control diabetes during pregnancy although confirmatory studies are still needed. CONCLUSION Experimental and clinical evidence support the supposition that the modulation of the gut microbiota via probiotic microorganisms could be effective in the prevention of gestational diabetes mellitus.
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Impact of nutritional supplementation during pregnancy on antibody responses to diphtheria-tetanus-pertussis vaccination in infants: A randomised trial in The Gambia.
Okala, SG, Darboe, MK, Sosseh, F, Sonko, B, Faye-Joof, T, Prentice, AM, Moore, SE
PLoS medicine. 2019;(8):e1002854
Abstract
BACKGROUND Exposure to a nutritionally deficient environment during fetal life and early infancy may adversely alter the ontogeny of the immune system and affect an infant's ability to mount an optimal immune response to vaccination. We examined the effects of maternal nutritional supplementation during pregnancy on infants' antibody responses to the diphtheria-tetanus-pertussis (DTP) vaccine included in the Expanded Programme on Immunisation (EPI). METHODS AND FINDINGS The Early Nutrition and Immune Development (ENID) trial was a randomised, partially blinded trial conducted between April 2010 and February 2015 in the rural West Kiang region of The Gambia, a resource-poor region affected by chronic undernutrition. Pregnant women (<20 weeks' gestation) with a singleton pregnancy (n = 875) were randomised to receive one of four supplements: iron-folic acid (FeFol; standard of care), multiple micronutrient (MMN), protein-energy (PE), or PE + MMN daily from enrolment (mean [SD] 13.7 [3.3] weeks' gestation) until delivery. Infants were administered the DTP vaccine at 8, 12, and 16 weeks of age according to the Gambian Government protocol. Results for the primary outcome of the trial (infant thymic size) were described previously; here, we report on a secondary outcome, infant antibody response to vaccination. The effects of supplementation on mean DTP antibody titres measured in blood samples collected from infants at 12 weeks (n = 710) and 24 weeks (n = 662) were analysed with adjustment for confounders including maternal age, compliance to supplement, and infant sex and season. At 12 weeks, following a single dose of the vaccine, compared with FeFol (mean 95% confidence interval [CI]; 0.11 IU/mL, 0.09-0.12), antenatal supplementation with MMN or MMN + PE resulted in 42.4% (95% CI 20.1-64.6; p < 0.001) and 29.4% (6.4-52.5; p = 0.012) higher mean anti-diphtheria titres, respectively. Mean anti-tetanus titres were higher by 9.0% (5.5-12.5), 7.8% (4.3-11.4), and 7.3% (4.0-10.7) in MMN, PE, and PE + MMN groups (all, p < 0.001), respectively, than in the FeFol group (0.55 IU/mL, 0.52-0.58). Mean anti-pertussis titres were not significantly different in the FeFol, MMN, and PE + MNN groups but were all higher than in the PE group (all, p < 0.001). At 24 weeks, following all three doses, no significant differences in mean anti-diphtheria titres were detected across the supplement groups. Mean anti-tetanus titres were 3.4% (0.19-6.5; p = 0.038) higher in the PE + MMN group than in the FeFol group (3.47 IU/mL, 3.29-3.66). Mean anti-pertussis titres were higher by 9.4% (3.3-15.5; p = 0.004) and 15.4% (9.6-21.2; p < 0.001) in PE and PE + MMN groups, compared with the FeFol group (74.9 IU/mL, 67.8-82.8). Limitations of the study included the lack of maternal antibody status (breast milk or plasma) or prevaccination antibody measurements in the infants. CONCLUSION According to our results from rural Gambia, maternal supplementation with MMN combined with PE during pregnancy enhanced antibody responses to the DTP vaccine in early infancy. Provision of nutritional supplements to pregnant women in food insecure settings may improve infant immune development and responses to EPI vaccines. TRIAL REGISTRATION ISRCTN49285450.
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Maternal HIV and Paediatric Lung Health.
Slogrove, AL, Frigati, L, Gray, DM
Paediatric respiratory reviews. 2017;:47-53
Abstract
With improved prevention of mother to child transmission of HIV, paediatric HIV disease is less common. However, the number of HIV exposed but uninfected infants is growing. Exposure to maternal HIV impacts infant respiratory health through an increase in known risk factors such as increased preterm birth and low birth weight, suboptimal breastfeeding, increased psychosocial stressors and increased exposure to infective pathogens. Exposure to the HIV virus and altered maternal immune environment result in immunologic changes in the infant that may contribute to respiratory disease risk. HIV exposed infants are at increased risk for severe pneumonia with poorer outcomes compared to unexposed infants. Maternal ART and optimal nutrition, including breastfeeding in high infective disease burden settings, reduce morbidity and mortality in HIV exposed infants and should be prioritized. The impact of exposure to maternal HIV on normal lung growth and risk for chronic respiratory disease is unknown and warrants further investigation.
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The mother-offspring dyad: microbial transmission, immune interactions and allergy development.
Jenmalm, MC
Journal of internal medicine. 2017;(6):484-495
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Abstract
The increasing prevalence of allergy in affluent countries may be caused by reduced intensity and diversity of microbial stimulation, resulting in abnormal postnatal immune maturation. Most studies investigating the underlying immunomodulatory mechanisms have focused on postnatal microbial exposure, for example demonstrating that the gut microbiota differs in composition and diversity during the first months of life in children who later do or do not develop allergic disease. However, it is also becoming increasingly evident that the maternal microbial environment during pregnancy is important in childhood immune programming, and the first microbial encounters may occur already in utero. During pregnancy, there is a close immunological interaction between the mother and her offspring, which provides important opportunities for the maternal microbial environment to influence the immune development of the child. In support of this theory, combined pre- and postnatal supplementations seem to be crucial for the preventive effect of probiotics on infant eczema. Here, the influence of microbial and immune interactions within the mother-offspring dyad on childhood allergy development will be discussed. In addition, how perinatal transmission of microbes and immunomodulatory factors from mother to offspring may shape appropriate immune maturation during infancy and beyond, potentially via epigenetic mechanisms, will be examined. Deeper understanding of these interactions between the maternal and offspring microbiome and immunity is needed to identify efficacious preventive measures to combat the allergy epidemic.
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Early-Life Nutritional Programming of Health and Disease in The Gambia.
Moore, SE
Annals of nutrition & metabolism. 2017;(3):179-183
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Abstract
BACKGROUND Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. SUMMARY We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality.
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Breastfeeding and perinatal exposure, and the risk of asthma and allergies.
Lodge, CJ, Dharmage, SC
Current opinion in allergy and clinical immunology. 2016;(3):231-6
Abstract
PURPOSE OF REVIEW Exposures during the perinatal period, a phase of rapid development, may have a profound and sustained effect on disease risk. In particular, perinatal exposures may influence the development and maturation of the infant immune system and the risk of allergic disease. We aimed to summarize the current literature on perinatal exposures and the risk of asthma and allergic disease RECENT FINDINGS Increased risk of offspring wheeze or asthma was found for: maternal obesity and hypertension during pregnancy; febrile illness, gynaecological, and viral respiratory infections in pregnancy; exposure to bisphenol A and phthalates in pregnancy and childhood; exposure to smoking in utero; low birth weight; caesarean section and neonatal hyperbilirubinaemia. Reduced risk of offspring atopic eczema was found for hookworm infection in pregnancy and reduced risk of offspring wheeze was associated with increased pregnancy dietary intake of vitamin E and zinc. Higher levels of selenium in pregnancy were associated with less risk of asthma in genetically susceptible offspring. Early life pet ownership was associated with a decrease in atopic asthma but an increase in nonatopic asthma risk. SUMMARY A diverse range of exposures were associated with allergic disease risk, highlighting the susceptibility of children during the perinatal period. Clinicians should reinforce public health messages concerning maternal obesity, smoking, and breastfeeding. The infant gut microbiome is emerging as an important hypothesis, which may mediate the relationship between many perinatal exposures and allergic disease.
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In-utero exposures and the evolving epidemiology of paediatric allergy.
Khan, TK, Palmer, DJ, Prescott, SL
Current opinion in allergy and clinical immunology. 2015;(5):402-8
Abstract
PURPOSE OF REVIEW Emerging evidence suggests that the rising prevalence of early-onset 'noncommunicable' diseases, such as paediatric atopy, is related to modern environmental changes, the effects of which appear to commence in utero or even preconception. Here, we review how recent publications have contributed further to our understanding of the influence of in-utero exposures on the predisposition to immune dysregulation, with a particular focus on the evolving epidemiology of paediatric allergy. RECENT FINDINGS New evidence suggests that inter-individual variations in immune function development are principally driven by nonheritable factors, for example periconceptional environment. One of the most significant influences is maternal nutrition during pregnancy. New studies further support a healthy balanced maternal diet that contains immunomodulatory nutrients, prebiotics and probiotics, which benefit multiple aspects of fetal development, including immune development. In addition, declining maternal biodiversity, maternal stress and exposures to environmental pollutants further interact to have adverse influences on the developing immune system. SUMMARY The in-utero period appears to be a critical time point. Further investigations of gene-environmental interaction mechanisms are essential prior to further recommendations of early-life preventive strategies to reduce the growing global burden of allergic disease, as well as other 'noncommunicable' diseases.
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Recent advances in the epidemiologic investigation of risk factors for asthma: a review of the 2011 literature.
Antó, JM
Current allergy and asthma reports. 2012;(3):192-200
Abstract
The present review aims to identify and summarize epidemiologic investigations published during 2011 on the environmental risk factors for asthma. Potentially eligible papers were identified by a MEDLINE search. In total, 1,130 items were retrieved. Based on a broad definition of environment, the following topics were included: obesity, diet, vitamin D, air pollution, farming environment, and social factors. Some of the more relevant contributions included evidence that 1) obesity precedes asthma, 2) fruit consumption is longitudinally associated with a lower risk of asthma and atopy, 3) a comprehensive statewide smoking ban was followed by a reduction in hospital admissions for asthma, 4) asthma is one of the diseases showing the largest burdens due to environmental tobacco smoke, 5) traffic-related urban air pollution is associated with bronchial inflammation as measured by fractional exhaled nitric oxide and uncontrolled asthma, 6) aeroallergens and desert dust may contribute to the short-term effects of air pollution and asthma, and 7) maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring.
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Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial.
Boyle, RJ, Ismail, IH, Kivivuori, S, Licciardi, PV, Robins-Browne, RM, Mah, LJ, Axelrad, C, Moore, S, Donath, S, Carlin, JB, et al
Allergy. 2011;(4):509-16
Abstract
BACKGROUND Probiotic supplementation in early life may be effective for preventing eczema. Previous studies have suggested that prenatal administration may be particularly important for beneficial effects. OBJECTIVE We examined whether prenatal treatment with the probiotic Lactobacillus rhamnosus GG (LGG) can influence the risk of eczema during infancy. METHODS We recruited 250 pregnant women carrying infants at high risk of allergic disease to a randomized controlled trial of probiotic supplementation (LGG 1.8 × 10(10) cfu/day) from 36 weeks gestation until delivery. Infants were assessed during their first year for eczema or allergic sensitization. Immunological investigations were performed in a subgroup. Umbilical cord blood was examined for dendritic cell and regulatory T cell numbers and production of TGFβ, IL-10, IL-12, IL-13, IFN-γ and TNFα. Maternal breast milk was examined for total IgA, soluble CD14 and TGFβ. RESULTS Prenatal probiotic treatment was not associated with reduced risk of eczema (34% probiotic, 39% placebo; RR 0.88; 95% CI 0.63, 1.22) or IgE-associated eczema (18% probiotic, 19% placebo; RR 0.94; 95% CI 0.53, 1.68). Prenatal probiotic treatment was not associated with any change in cord blood immune markers, but was associated with decreased breast milk soluble CD14 and IgA levels. CONCLUSIONS Prenatal treatment with Lactobacillus rhamnosus GG was not sufficient for preventing eczema. If probiotics are effective for preventing eczema, then a postnatal component to treatment or possibly an alternative probiotic strain is necessary.